A study is in progress to elucidate the mechanism by which methadone and other opioids produce growth retardation. Biochemical methods are used to quantify deficits in RNA and protein biosynthesis. In addition we are undertaking an electronmicroscopical evaluation of affected tissues. Neonatal mice are injected daily with small dosages of dl-methadone or other opioid. Dose-related decreases in weight gain are noted which appear to be related to metabolic deficits in protein synthesis. The precise way in which the metabolic deficit is induced is unknown but may involve RNA synthesis. We plan to investigate nucleic acid metabolism in the hope of finding the basis for the protein synthesis deficit. Salamanders are also used in our studies because regenerating limbs represent total replacement of tissues of diverse origin. This regneration process was found to be highly sensitive to opioids, an effect that can be blocked by naloxone. BIBLIOGRAPHIC REFERENCES: Hui, F., Krikun, E., Hirsh, E., Blaiklock, R., and Smith, A., Inhibition of nucleic acid synthesis in the regenerating limb of salamanders treated with methadone or narcotic antagonists. Exptl. Neurol. 53: 276-283, 1976. Smith, A., Englesher, C., and Crofford, M., Respiratory or analgesic actions of ethanol and other narcotics: modulation by biogenic amines, Ann. N.Y. Acad. Sci. 273: 256-262, 1976.